The focus of this research is to define immunologic and other cofactors to explain why cervical HPV infection (a common sexually-transmitted diseases) progresses in rare instances to high-grade neoplasia. Accompanying prevention research on HPV immunology attempts to complement ongoing worldwide vaccine development efforts by suggesting biomarkers correlated with good clinical outcomes following infection (i.e., natural protection). Several immunology projects were completed. A large, cross-sectional investigation of cellular immune responses to the transforming proteins of HPV (E6 and E7) demonstrated that women with serious neoplasia had lower IL-2 production than HPV-infected women who did not develop serious neoplasia. Thus, high IL-2 production might be a useful marker of successful host control of HPV infection (the "Th1 response"). With regard to serologic measurements of immune response, the virus-like particle (VLP) assay was confirmed to be a useful epidemiologic biomarker of infection. Although not as sensitive as DNA testing for current infection, the VLP assay permits some measurement of infections no longer detectable by HPV DNA testing. Thus, an examination of VLP seropositivity among HPV DNA-negative women demonstrated a strong association with past sexual activity. HPV serology can now be used in studies where tissue specimens are not available. In a study in China, penile cancer was found not to be HPV-related. In the U.S., vulvar cancer was shown to be divisible into HPV-related and non-related histologic subtypes. Serology tests suggested that there are at least two distinct patterns of responses to HPV among women with cervical neoplasia. Serologic and cellular assays are now being tested in prospective studies.